Welcome to our European Regulatory Roundup, our weekly overview of the top EU regulatory news.
EMA Finalizes Guidelines on Using Patient-Reported Outcomes in Oncology Trials
The European Medicines Agency (EMA) has finalized its guidelines on the use of patient-reported outcomes (PRO) in oncology clinical trials. EMA created the document to help sponsors incorporate patient perspectives and quality-of-life measures into their clinical trial datasets.
Once the document comes into force at the start of November, sponsors will have a set of scientific best practices they can follow when considering how to gather PROs. EMA sees value in using PROs to support conclusions regarding treatment effects, the risk-benefit balance and specific therapeutic claims, but thinks certain principles must be followed to ensure the data are unbiased. The principles communicated in the guidelines give sponsors leeway to select the approach that is most appropriate for their trials, rather than forcing them to use particular processes and techniques.
Before applying the principles to the selection of PRO instruments and processes, EMA is asking sponsors to consider whether it is appropriate to gather such outcomes data. The first of 12 general recommendations listed by EMA speaks to this point by encouraging sponsors to assess the extent to which “PRO measures can provide added value in the clinical trial setting.” Subsequent points raised by EMA ask sponsors to consider whether the PRO data can “detect meaningful effects,” “make a difference to the study” or affect the “regulatory benefit risk balance assessment.”
This thought process should start before a company is nearing late-phase trials, at which point the time to start developing a dedicated instrument may already have passed. EMA has opted against taking a prescriptive approach to the selection of PRO instruments, a stance it adopted after deciding the breadth of the topic was beyond the scope of its document. Instead, EMA has highlighted some concepts sponsors should consider when selecting an instrument, such as the evidence to suggest the best tools are developed in collaboration with patients.
Having decided to gather a PRO in a study, sponsors are advised to incorporate the measure in their protocols as early in the development of the documents as possible. At this stage, EMA’s general recommendations on best practices for collecting PROs start to apply. The regulator recommends PRO measures be collected at the start of a participant’s visit to a trial site whenever possible. This approach lessens the risk that information the participant learns during the site visit or the effect of immediate toxicities from chemotherapy will bias their responses.
Final Guideline, Press Release
CHMP Posts Draft Concept Paper on Pediatric Clinical Trials of Antibacterials
The Committee for Human Medicinal Products (CHMP) has released a draft concept paper on trialing antibacterial treatments in pediatric populations. CHMP expects the concept paper will lead to the publication of draft guidelines designed to fill a gap in the current regulations within the next year.
As it stands, the regulatory advice in the Guideline on the Evaluation of New Anti-bacterial Medicinal Products lacks a full evaluation of the specific needs of pediatric populations. EMA’s Infectious Diseases Working Party (IDWP) has identified four situations the current guidelines fail to cover, including how to approach the development of antibacterials against infections that exclusively or mainly affect children. When developing antibacterials against such infections, the traditional, adult-first model of clinical trials is flawed.
IDWP also sees a need for specific advice on how to handle drugs against infections that have the same etiology and pathogenesis in all age groups. The working group thinks extrapolation of efficacy data from adults to children can be acceptable in such instances. The other two situations singled out by IDWP as necessitating new regulations relate to antibacterials that have undergone limited testing in adults because of the high unmet need, and those that are absorbed at levels so low that it is impossible to derive pediatric dosing from adult pharmacokinetic data.
Having identified these gaps in the current regulations, IDWP has begun thinking about the extent to which data extrapolation from adults to children is possible in each of the scenarios. IDWP is also assessing the need to run dedicated pharmacokinetic studies in each pediatric age group prior to the start of safety and efficacy trials, as well as the best way to design the latter type of research program. CHMP has given interested parties until the end of June to comment on these questions and the other points raised in the concept paper.
The consultation timeline is seen as enabling IDWP to have a draft addendum on the topic ready for release in the first quarter of next year. If IDWP hits this timeline, the expectation is that the document would be finalized before the end of 2017.
DNA Vaccine Recommended for Approval by EMA for the First Time
EMA has recommended the approval of a DNA vaccine for the first time to protect Atlantic salmon from salmon pancreas disease (SPD). The vaccine consists of a genetic sequence that stimulates a protective immune response by triggering the production of proteins.
Before making the recommendation, EMA’s Committee for Medicinal Products for Veterinary Use (CVMP) looked into the environmental risks of introducing the novel vaccine. The assessment led the committee to conclude that the risk to the environment is negligible. In addition, research shows any residues of the vaccine degrade quickly in the gastrointestinal tract of the salmon, resulting in the fish being deemed to be safe to eat.
The applicant, Elanco, backed up these safety data with evidence of the efficacy of the vaccine. When administered to salmon via intramuscular injections in fresh and seawater trials, the vaccine was associated with a decline in mortality and a reduction in the damage to the heart, pancreas and muscle tissue that characterizes SPD. CVMP concluded that the data amounted to evidence that the vaccine is clinically relevant and provides direct benefit to the health and welfare of salmon.
In reaching this conclusion, CVMP has delivered a boost to Elanco and other developers of DNA vaccines, while also providing more evidence of the value of its minor use minor species (MUMS) regulatory pathway. EMA created the MUMS category to encourage the development of treatments for veterinary diseases that represent a small market opportunity.
Press Release, More
EMA has released a guide to avoiding medication errors when using iron-removal drug Exjade. The regulator created the educational materials in response to concerns that the introduction of a new dosage form could lead to medication errors. In the guide, EMA outlines the different dosing regimens for the film-coated and dispersible versions of the drug to patients and doctors. Educational Material
CHMP and CVMP have updated a question and answer document on drug quality. The new material relates to the data that are needed for sterilization processes of primary packaging materials that are destined for use in aseptic manufacturing processes. The addition of the topic follows shortly after CHMP and CVMP proposed revised guidelines on the sterilization of primary containers. Q&A
The United Kingdom Medicines and Healthcare Products Regulatory Agency (MHRA) has seized more than 62,000 doses of unlicensed erectile dysfunction medicines. MHRA enforcement officers discovered the products during raids on properties in Scunthorpe. MHRA Notice
In a separate release, MHRA has asked life raft owners to check if their first aid kits contain unauthorized Chinese medicines. MHRA Alert